Iwasaki Mio, Kawahara Yuka, Okubo Chikako, Yamakawa Tatsuya, Nakamura Michiko, Tabata Tsuyoshi, Nishi Yohei, Narita Megumi, Ohta Akira, Saito Hirohide, Yamamoto Takuya, Nakagawa Masato, Yamanaka Shinya, Takahashi Kazutoshi
Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
iPSC-Based Drug Discovery and Development Team, RIKEN Bio Resource Research Center (BRC), Kyoto, Japan.
iScience. 2022 Apr 25;25(5):104289. doi: 10.1016/j.isci.2022.104289. eCollection 2022 May 20.
The effects of transcription factors on the maintenance and differentiation of human-induced or embryonic pluripotent stem cells (iPSCs/ESCs) have been well studied. However, the importance of posttranscriptional regulatory mechanisms, which cause the quantitative dissociation of mRNA and protein expression, has not been explored in detail. Here, by combining transcriptome and proteome profiling, we identified 228 posttranscriptionally regulated genes with strict upregulation of the protein level in iPSCs/ESCs. Among them, we found 84 genes were vital for the survival of iPSCs and HDFs, including 20 genes that were specifically necessary for iPSC survival. These 20 proteins were upregulated only in iPSCs/ESCs and not in differentiated cells derived from the three germ layers. Although there are still unknown mechanisms that downregulate protein levels in HDFs, these results reveal that posttranscriptionally regulated genes have a crucial role in iPSC survival.
转录因子对人诱导多能干细胞或胚胎多能干细胞（iPSC/ESC）的维持和分化的影响已得到充分研究。然而，导致mRNA和蛋白质表达量解离的转录后调控机制的重要性尚未得到详细探讨。在这里，通过结合转录组和蛋白质组分析，我们在iPSC/ESC中鉴定出228个转录后调控基因，其蛋白质水平有严格上调。其中，我们发现84个基因对iPSC和人成纤维细胞（HDF）的存活至关重要，包括20个iPSC存活特别必需的基因。这20种蛋白质仅在iPSC/ESC中上调，而在源自三个胚层的分化细胞中未上调。尽管仍存在下调HDF中蛋白质水平的未知机制，但这些结果表明转录后调控基因在iPSC存活中起关键作用。
